Vibrio cholera is a human pathogen that colonizes the gut and elicits both mucosal and systemic protective immune responses. Novel SIV prophylactics will be developed using a genetically attenuated strain of this organism to derive oral SIV vaccines. These new oral vaccines will be evaluated in animals for their immunogenicity. As a component of the Collaborative Mucosal Immunology Group for AIDS vaccine (CMIG, AI35544), these vaccines will be evaluated in primates for their immunogenicity and protective efficacy using the SIV primate model. This study will provide essential databases for developing HIV prophylactics and for conducting human trials. Considering the disastrous spread of HIV population in developing countries in Africa and in Asia, effective and inexpensive oral HIV1 vaccines may be the only way to stop the AIDS pandemic.